Salts of carbamic and thiocarbamic esters with fungicidal and fungistatic action

ABSTRACT

SALTS OF CARBAMIC AND TIOCARBAMIC ESTERS ARE USED HAVING FUNGICIDAL AND FUNGISTATIC ACTION, SAID SALTS HAVING THE GENERAL FORMULA   (CH3-)2-N-(CH2)N-NH-CO-X-R   WHEREIN R IS AN ALIPHATIC HYDROCARBON RADICAL WITH PREFERALY 2 TO 4 CARBON ATOMS, X IS OXYGEN OR SULFUR, AND N IS AN INTEGER FROM 2 TO 4 WITH AN INORGANIC OR ORGANIC ACID.

United States Patent 3,649,674 SALTS 0F CARBAMIC AND THIOCARBAMIC ESTERS WITH FUNGICIDAL AND FUNGI- STATIC ACTION Georg-Alexander Boyer and Ernst Albrecht Pieroh, Berlin, Germany, assignors to Schering AG, Berlin and Bergkamen, Germany No Drawing. Filed July 18, 1968, Ser. No. 746,711 Claims priority, application Germany, Aug. 25, 1967, P 16 43 040.3 Int. Cl. C07c 125/06 US. Cl. 260482 C 17 Claims ABSTRACT OF THE DISCLOSURE Salts of carbamic and thiocarbamic esters are used having fungicidal and fungistatic action, said salts having the general formula -(CH2) n NH-C OXR wherein R is an aliphatic hydrocarbon radical with preferably 2 to 4 carbon atoms, X is oxygen or sulfur, and n is an integer from 2 to 4, with an inorganic or organic acid.

The invention relates to new salts of N-(dialkylaminoalkyl)-carbamic esters and N-(dialkylaminoalkyl)-thiocarbamic esters with fungicidal and fungistatic action.

It has been found that salts of compounds of the general formula N-(CHz) r-NH-C O-X-R wherein:

R is an aliphatic hydrocarbon radical with preferably 2 to 4 carbon atoms,

X is oxygen or sulfur and n is an integer from 2 to 4, with any inorganic or organic acids exhibit a fungicidal and fungistatic action and therefore are suitable preferably for the control of phytopathogenic fungi.

In the above stated general formula, the radical R may have, among others, the following meaning: straight-chain or branched, saturated or unsaturated aliphatic hydrocarbon radicals, such as ethyl, propyl, butyl, isopropyl, tertiary butyl, allyl.

As suitable acids in connection with the invention there enter into consideration any inorganic or organic acids. Examples are generally mineral acids, monoor poly-carboxylic acids and sulfonic acids. Of the above the following may be specifically named: Hydrochloric acid, sulfuric acid, formic acid, propionic acid, valeric acid, oxalic acid, malonic acid, succinic acid, cyanoacetic acid, chloroacetic acid, dichloroacetic acid, trifiuoroacetic acid, benzoic acid, furane-Z-carboxylic acid, p-toluolsulfonic acid, methane-sulfonic acid, thioglycotic acid and citric acid, among others.

The salts according to the invention display an excellent fungicidal and fungistatic action and herein are surprisingly superior, to the best heretofore known compounds of the same direction of action. In particular, germination exciters, such as Pythium ultimum, are controlled. Another advantage is their excellent plant tolerance. In addition, their good solubility in water and their fitness for the production of dry disinfectants should be stressed, as

3,649,674 Patented Mar. 14, 1972 some of the salts are crystalline substances and others highly viscous oils.

They can therefore be used in agriculture or in horticulture predominantly for general soil treatment, as disinfectants for seed treatment or for furrow treatment as till-in material. The salts according to the invention may be used alone or as mixtures with one another or with other plant protecting or pest controlling agents, e.g., with insecticides or nematocides, when the simultaneous control of these or other pests is desired, or 'with fungicides to enlarge the spectrum of action. :Application of the invention is effected advantageously as powder, dust granulate, solution, emulsion or suspension, among others, with addition of solid or liquid diluents or vehicles and possible of adhesion, wetting, emulsification or dispersion aids. Use in the form of their aqueous solutions is likewise possible.

Suitable liquid vehicles for use with the invention are water, mineral oils or other organic solvents, as for example Xylol, chlorobenzene, cyclohexanol, cyclohexanone, dioxane, acetonitrile, acetic ester, dimethyl formamide and dimethyl sul-foxide, among others.

Solid vehicles such as lime, attaclay and other clays, kaolin, talcum as well as natural or synthetic silica among others, are suitable for use.

Surface-active substances may be used; such as salts of ligninsulfonic acids, salts of alkylated benzenesulfonic acids, sulfonated acid amides and their salts, polyethoxylated amines and alcohols.

If the active substances are to be used for seed disinfection, dyes, as for example new fuchsine among others, may be admixed, to give the disinfected seed material a clearly visible color.

The production of the various forms of preparation is carried out in a manner known in the art; such as, by grinding or mixing processes.

To promote germination of the seed, the agents are applied in a well known manner either before sowing directly onto the seed material or upon sowing into the furrow (so called tilling-in). For treatment of the soil in itself, the agents are advantageously introduced into the upper soil layers to a depth of about 20 cm., by the use, for example of a rotary hoe.

It is to be noted that the salts according to the invention are believed new and having not been described in the literature before. The production of the compounds herein is accomplished by methods for example as follows:

(a) A compound of the general formula wherein:

R is an aliphatic hydrocarbon radical with preferably 2 to 4 carbon atoms,

X, oxygen or sulfur and n, an integer from 2 to 4, is neutralized with the desired acid hereinabove indicated in the usual manner or,

(b) The acid radical of any salt of the named compounds is exchanged for the desired acid radical by double conversion of two salts, or

(c) The ester radical R of any salt of the named compounds is exchanged for the desired ester radical R by ester interchange, or

(d) A compound of the general formula CHa N-(CH2)nNHa or the salt thereof with a hydrohalic acid is reacted with chloroformic esters of the general formula ClCOOR or carbonic esters of the general formula R'OCOOR wherein the reactions described under (c) and (d) the symbols R and n have the above-mentioned meaning and R is any hydrocarbon radical.

Reactions (a), (b) and (d) above are preferably carried out with the use of a solvent, such as water or organic solvents, such as ether, alcohol, hydrocarbons and hydrocarbon halides. For reaction the alcohol with the desired ester radical is used in excess.

Reactions (a) and ((1) may be carried out without solvent.

The reaction temperatures may be selected as desired and depend on the type of the reaction partners. They are approximately within the range of from '--20 to 100 deg. C. The isolation of the salts formed is likewise effected according to methods known such as by suctionfiltering the resultant crystals formed, by decanting the supernatant solutions from the precipitated oils, or by concentrating the solutions to dryness.

The following illustrative but not restrictive examples will explain some production processes used in accordance with the desired products of the invention.

(1) N-(3-dimethylammoniopropyl)-thiocarbamic acid- S-ethyl ester chloride 14.25 g. (0.075 mole) of N-(3-dimethylaminopropyl)- thiocarbamic acid-S-ethyl ester are dissolved in 250 ml. of absolute ether. While stirring and cooling, dry 1101 gas is introduced. After 1 hour the product is suction-filtered. One obtains 14.1 g. (83.4% of the theory) of the M.P. 879-3 deg. C. After reprecipitation from isopropanol/ ether one obtains a product of the M.P. 93-94 deg. C.

(2) N-(3-dimethylammoniopropyl)-carbamic acid propylester-hydrogen sulfate 11.0 g. (0.0585 mole) of N-(3-dimethylaminopropyl)- carbamic acid propylester are dissolved in 200 m1. of ether. While stirring and cooling, 3.2 ml. (0.06 mole) of concentrated sulfuric acid are added in drops. Agitation is continued for 2 hours at room temperature, the ether is decanted, the oil is washed with ether and dried in vacuum. One obtains 15.0 g. (89.7% of the theory) of the M.P. 4450 deg. C.

(3) N-(3-dimethylammoniopropyl)-carbamic acid propylester benzoate 14.1 g. (0.075 mole) of N-(dimethylaminopropyD- carbamic acid propylester are dissolved in 200 ml. of ether. While stirring, 9.15 g. (0.075 mole) of benzoic acid in ml. of tetrahydrofurane are added in drops. Agitation is continued for 2 hours, the solvent is distilled, and the oil dried in vacuum. One obtains 23.1 g. (99.4% of the theory) of n =1.5070.

*(4) N-(3-dimethylammoniopropyl) carbamic acid ethyl ester chloride 7 27.2 g. (0.1 mole) of N-(3-dimethylammoniopropyl)- carbamic acid ethyl ester hydrogen sulfate are dissolved in ml. of water and while stirring slowly admixed with a solution of 24.4- g. (0.1 mole) of BaCl 2H O in ml. of water. Agitate for 15 minutes, admix with 100 ml. of ethanol, suction filter the precipitated BaSO treat the aqueous solution with active carbon, filter, concentrate, and drag in vacuum. 1

One obtains 14.7 g. of oil of n =1.4900.

(5) N-(S-dimethylammoniopropyl)-carbamic acid butyl ester chloride 21.0 g. (0.1 mole) of N-(3-dimethylammoniopropyl)- carbamic acid ethyl ester chloride are suspended in 100 ml. of n-butanol. Dry HCl gas is introduced into the suspension for a shorttime and the mixture is heated for 6 hours at 100 to 115 deg. C. while stirring, the hydrochloride going into solution and some ml. of liquid distilling off. Then concentrate and drag the residue in vacuum. One obtains 18.0 g. of 115 14750.

(6) N-(3-dimethylammoniopropyl)-carbamic acid butyl ester chloride 4.6 g. (0.2 g.-atom) of sodium are dissolved in 200 ml. of n-butanol. To this add 21.0 g. (0.1 mole) of N-'(3 dimethylammoniopropyl) carbamic. acid ethyl ester chloride and boil the mixture for 6 hours with reflux. Concentrate, admix with water, ether out, dry the ether phase over MgSO introduce dry HCl gas While stirring and cooling, decant the ether solution, and drag the remaining oil in vacuum. One obtains 13.1 g. of n =1.4735.

(7) N-(3-dimethylammoniopropyl)-thiocarbamic acid- S-ethyl ester chloride I 12.25 g. (0.1 mole) of chlorothioformic acid-S-ethyl ester are dissolved in 50 ml. of absolute ether. While stirring, 10.2 g. (0.1 mole) of N,N-dimethyl propendiamine-(1,3) in 100 ml. of ether are slowly added in drops at 30 to 36 deg. C. After 1 hour of further agitation, suction-filter. One obtains 22.0 g. of the melting point -94 deg. C.

(8) N-(3-dimethylammoniopropyl)-carbamic ethyl ester chloride 20.4 g. (0.2 mole) of N,N-dimethylpropandiamine (1,3) are boiled with 80 ml. of diethyl carbonate for 3 hours with reflux. Then one distills the mixture and obtains 5.2 g. of N-(3-dimethylaminopropyl)-carbamic acid ethyl ester, B.P. l23 deg. C., n =1.4480. The product is dissolved in ml. of absolute ether, dry HCl gas is introduced, the ether solution is decanted, and the remaining oil is dragged in vacuum. One obtains 5.9 g. of n =l.49l5. I H

The other compounds herein following can be obtained in an analogous manner.

The following table shows additional salts according to the invention. l

acid

Physics I Name of compound constant;

1. N-(3-dimetl1ylammoniopropyD-carbamic acid ethyl ester chloride 7213 1.4915 2. I-(S-dimethylammoniopropyl) carbamic acid ethyl ester benzoate 1.5080 3. N -(3-d.imethylammoniopropyl) -earbarnic acid propyl ester chloride 20191865 4. N-(3-d1methylammoniopropyl)-carbamicacidpropyl ester formats 1113314600 5. N-(3 dlmethylammoniopropy1)-earbamic acid propyl ester propionate 01.9 1.4390 6. N-(3-dimethylammoniopropyl)-carbamic acidpropyl. ester valet-ate an 1.4440 7. N-(3-dhnethylammoniopropyl)-carbamic acid pro- .1 pylester hydrogenoxalaten 8. N-(3-dimethylammoniopropyl)-carbamic acid pro pylester malonate my 1.4675 9. N-(3-dimethy1ammoniopropyl)-carbamic acid pro- I pylcster succinate; my 1.4700 10. N-(3-dimethyiammoulopropyl)-carbamlc acid 'pro-, pylester cyanaoetata V 20 1 4552 11. N-(3-dimethyl oniopropyD-carbamic acid propylester chloroacptatc 1213 1.4740 12. N-(3-dimcthylammoniopropyl)-carbamlc acid propylester dichloro m) 1.4675 13. N-(3-dimcthylanunonlopropylrcarbamiti acid pro. pylester trifluoracetate 12 1.4245 14. N-(3-dimethylammoniopropylycarbamlc furane-Z- carboxylate 7113 1.4860 16. N43-dimethyiammoniopropyl)-carbamlc acid propylester-p-toluolsulionatez 711329 1.5000 16. N-(3-d1mcthylammoniopropy1) arbamlc acid butylcster chloride my 1.4729 17. N-(3-dimethylammoniopropyl)-thiccarbamic acid- S-propylester chloride my 1.5210

The above noted compounds are usually crystalline substances or highly viscous oils. They are soluble in water, methanol and ethanol among others.

The starting products for the production of the salts according to the invention can likewise be produced by methods such as by conversion of a dimethylaminoalkylamine with a corresponding chloroformic ester or thioester in a suitable solvent, per se or in the presence of an acid acceptor. As solvents there may serve for this purpose, inert organic liquids, such as ether or hydrocarbons. Suitable acid acceptors are for example tertiary organic amines, such as triethylamine or pyridine among others, inorganic bases, such as alkali hydroxides or carbonates among others, or the amine required for the conversion, which is then used in correspondingly greater quantity. The reaction proceeds smoothly in a temperature range of approximately to 100 deg. C., but can be carried out as a single phase or two-phase reaction, the latter with the use of nonmiscible liquids, such as water and organic solvent.

In the following, some starting products are described:

N-(gamma-dimethylaminopropyl)-thiocarbamic acid S-ethyl ester Undistillable oil N-(gamma-dimethylaminopropyl)-carbamic acid ethyl ester B.P.( mm.) 121-124 N-(gamma-dimethylaminopropyl)- B P 3 mm.) 139-141 carbarnlc acid propyl ester degrees 0. H19 =1.4490.

N-(gamma-dirnethylaminopropyl)- carbamic acid butyl ester B.P.(1s mm.) 146-148 degrees 0. 121320 =1.4505

The following examples will explain the action and use of the salts according to the invention.

EXAMPLE 1 Root rate:

4=white roots without fungus necroses 3=white roots, slight fungus necroses 2=brown roots, more advanced fungus necroses 1=advanced fungus necroses, root rotted Active substance Number Root per liter of healthy rating of soil. mg. peas (1-4) Product used:

N-(3-dimethylammoniopropyD- 50 19 4 thiocarbamic acld-S-ethyl ester 100 20 4 chloride 200 24 4 N-(3-dimethylam1noniopropyD- 50 11 3 carbamic acid propylester 100 16 4 hydrogen oxalate 200 22 4 N-(B-dimethylammoniopropyD- 50 18 4 carbamic acid propylester 100 19 4 formats 200 18 4 CAPTAN 50 4 1 100 6 1 200 13 1 Steamed soil (3 control tests):

Untreated soil (3 control tests):

EXAMPLE 2 Steamed compost soil was inoculated with mycelium of Pythium ultimum. Peas of the variety Miracle of Kelvedon, disinfected with 50% product formulations were sowed 2-3 cm. deep in clay dishes holding 0.5 liter of soil; per concentration 25 grains. After a cultivation period of 14 days at 25-29 deg. C., the number of germinated healthy peas was determined. A comparison was made with the known products MANEB (manganeseethylene-bis-dithiocarbamate) and CAPTAN (N-trichloromethylthio-tetrahydrophthalimide) Number of germinated healthy peas 2.0 grams activ e substance 0.5 1.0 per kg Products used grams grams of seed N-(3dimethylammoniopropyl)-thio carbamic acid-S-ethylester chloride 21 24 24 N-(3-dimethylammoniopropyl)- carbamlc acid propylester hydrogen oxalate 19 18 20 N-(3-dimethylamrnoniopropyl) carbamic acid propylester tormate- 16 20 22 N-(3-dimethylammoniopropyl)- carbamic acid ethyl ester benzoate 5 19 18 N-(3-dimethylammoniopropyl) carbamic ethyl ester chloride 15 15 22 N-(3-dimethylammoniopropyl) carbamic acid propyl ester chloride.-. 3 9 23 N-(3-dimethylammoniopropyl)- carbamic acid butyl ester chloride- 4 9 24 N-(3-dimethylammoniopropyl)- carbamic acid propylester benzoate 13 21 25 IANE 1 8 6 CAPTAN 9 6 13 Steamed soil. A- 22 Seed without disinfect 24 (3 control tests). 0 25 Untreated soil. A 2 Seed Without disinfection. B 7 (3 control tests). 0 2

EXAMPLE 3 Disinfection experiment in the field Per product and concentration, there were sown 3 times 100 grains of marrow peas of the variety Sperlings Salout. The disinfection of the seed material was effected with 50% product formulations in powder form; the products being compared had a content of active substance of 92% (MANEB=manganese-ethylene-bis-dithiocarbamate) and (TMTD:tetramethyl-thiurem-disulfide). The germinated healthy peas were counted after a cultivation time of 14 days. The experiment was carried out at high soil temperatures (20-25 deg. C. in a depth of 10 cm.). Artificial irrigation by sprinkling was applied as needed. The following table contains the mean value from 3 tests with peas each.

7 What is claimed is: 1 A salt of thecompound of the general formula --=R is an alkyl from 2 to carbon atoms,

X is. oxygen, and n an integer from 2 to 4,

with any desired acid, said acid being selected from the group consisting of inorganic and of organic.

2. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid ethyl ester chloride.

3. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid ethyl ester benzoate.

4. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyD-carbamic acid propyl ester chloride.

5. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid propyl ester formate.

6. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid propyl ester propionate.

7. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid propyl ester valerate.

8. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid propyl ester hydrogen oxalate.

9. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid propyl ester malonate.

10. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylammonio; propyD-carbamic acid propylester succinate. '11. A compound having the general, formula as";set forth in claim 1 and which is N-(3-dimethylarnmoniopropyl)-carbamic acid propyl ester chloroacetate. v

12. A compound having the general formula as :set forth in claim 1 and which is N-(3-dimethylamrnonio propyl)-carbamic acid propyl ester dichloroacetate.

13. A compound having the general formula .as set forth in claim 1 and which is .N-(3-dimethylammonio,-. propyl)-carbamic acid propyl ester trifiuoroacetate.

14. A compound having the general formula as set forth in claim 1 and which is N-(3-dimethylamm0niopropyl)-carbamic acid propyl ester benzoatm 15. A compound having the general formula as se forth in claim 1 and which is N-(3-dimethylammonior propyl)-carbamic acid propyl ester-p-toluol-sulfonate.

16. A compound having thegeneral: formula as set forth in claim 1 and which is N-(3-dimethylammoniopropyl)-carbamic acid propyl ester hydrogen sulfate.

17. A compound having the general formula as set forth in claim 1 and which is N-(3-dime-thylammoniopropyl)-carbamic acid butyl ester chloride. 5

References Cited UNITED STATES PATENTS I 2,721,208 10/1955 Losee a a1. 2 0 482 X 3,243,389 3/1966 Moller 2601-482 X LORRAINE A. WEINBERGER, Primary Examiner P. KILLOS, Assistant Examiner I US. Cl. X.R. 

